Follicular Dendritic Cell Sarcoma of the Tonsil

Follicular dendritic cells belong to the accessory immune system, and they are normally present in the germinal center of primary and secondary follicles. Their major functions include serving as antigen-presenting cells and playing a major role in the induction and maintenance of the humoral immune response. Tumors featuring the characteristics of follicular dendritic cells were first described in four cases reported by Monda, et al.1 in 1986. Since then, approximately 70 cases have been reported, most of which are known to be of lymph node origin. However, 24 cases with an extranodal origin were identified in the head and neck region.2-9 To date, however, no Korean cases of tumors featuring the characteristics of follicular dendritic cells have been reported. We report a case of this rare entity which developed in the tonsil, in which the diagnosis and treatment were difficult. Here, we present our case with a review of the literature.

A 65-year-old male patient visited us with a 1-week-history of discomfort when swallowing food. A physical examination showed a 1×1 cm round mass on the surface of the right tonsil (Fig. 1). This mass had an irregular surface but had no necrotic or ulcerative areas. A neck examination revealed no enlarged lymph nodes. Diagnostic tonsillectomy was performed. There was no gross evidence of a residual tumor in the right tonsillar fossa after surgery. The resected right tonsillar tissue was 3×2×1.7 cm in size (Fig. 2).

Fig. 1
Preoperative endoscopic finding shows irregular round mass in right tonsil (superior view).

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Fig. 2
(A) Surgical specimen shows irregular round mass measuring 3×2×1.7 cm in size on right tonsil. (B) The tumor tissue consisted of spindle to ovoid cell proliferation forming fascicles, storiform patterns, and whorls. Individual neoplastic cells show elongated vesicular nuclei with distinct nucleoli, plump, slightly eosinophilic cytoplasm, and indistinct cell borders (HE stain ×400). (C) Immunohistochemical findings of the neoplastic cells are positive for CD21 (×400).

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Histopathological examination of the excised tonsil showed infiltrating tumor tissue and small intermingled residual lymphocytes. The tumor tissue consisted of spindle to ovoid cell proliferation forming fascicles, storiform patterns, and whorls, including 360 degree whorls. Individual neoplastic cells showed elongated vesicular nuclei with distinct nucleoli, plump, slightly eosinophilic cytoplasm, and indistinct cell borders (Fig. 2). Microcystic changes containing hemorrhage and occasional multinucleated cells were also seen. Mitotic figures were counted to 16/10 HPF. Immunohistochemical findings of the neoplastic cells are positive for CD21 and negative for CK, LCA, CD20, CD3, ALK-1, CD56, CD68, CD30, and S100 (Fig. 2). Based on histopathologic and immunohistochemical findings, the patient was diagnosed with follicular dendritic cell sarcoma (FDCS). Neck computed tomography (CT) and magnetic resonance image (MRI) after the tonsillectomy showed no remaining tumor and no abnormal findings on the surrounding structures. Subsequent staging with positron emission tomography/computed tomography of the neck, thorax, and abdomen revealed no regional or distant metastasis. Since this intermediate-grade malignancy is associated with a high risk of local recurrence, we prescribed radiotherapy at the primary site as adjunctive therapy. Postoperative radiotherapy of 5,400 cGy with 180 cGy fractions delivered over 6 weeks was applied to the right tonsillar region. The patient survived with a 2-year disease free period.

FDCS is a rare neoplasm arising not only from lymph nodes but also extranodally, either as acquired lymphoid tissue or as part of the organized constitutive lymphoid tissue. In most cases, the tumor occurs in the lymph nodes of the neck, mediastinum, and axilla. In approximately 30% of cases, the tumor develops in such extranodal sites as the liver, tonsil, and intra-abdominal soft tissue.10 A similar prevalence was seen between male and female patients, and the median age of the patients was 47 years with a wide age range of 14-77 years.11, 12 FDCS is typically described as a painless, slow-growing, well-circumscribed mass. A histopathological diagnosis of FDCS can be made homogeneously. Microscopically, FDCS is composed of oval to spindle cells with eosinophilic cytoplasm arranged in sheets, fascicles, and whorls, sometimes admixed with foci showing a storiform pattern of growth, suggesting a diagnosis of sarcoma. Tumor cells are typically characterized by mixtures of small lymphocytes, which can lead to a misdiagnosis of lymphoma. Immunophenotypes of FDCS are positive for CD21, CD35, Ki-M4p, and Ki-FDC1p, and are variably positive to vimentin, S-100 protein, CD68 and specific muscle actin (2, 10, 15, 16). Of these, CD21 and CD35 are the most useful antibodies because of their sensitivity and specificity. These antibodies can be used individually, and their sensitivity increases when they are used as a "cocktail".8 In the current case, microscopic findings were consistent with those above and were positive for CD21. This led to the diagnosis.

Differential diagnoses include extracranial meningioma, peripheral nerve sheath tumor, malignant melanoma, ectopic thymoma, metastatic carcinoma, malignant fibrous histiocytoma, large cell lymphoma, and interstitial reticulum cell sarcoma.8, 9 The diagnosis of FDCS can be made based on microscopic and immunohistochemical findings. In the immunohistochemical study of poorly differentiated tumors, however, markers for FDCS are not generally used. Therefore, in cases in which FDCS occurred in extranodal sites, the diagnosis of these rare tumors cannot be made easily.4, 6, 7

For the management of tonsillar FDCS, a wide excision of the tumor was performed. In cases in which metastasis to regional lymph nodes is suspected on imaging studies, a neck dissection is recommended.3 In the current case, a neck dissection was not performed because no findings suggestive of metastasis to the neck lymph nodes were observed on imaging studies following the diagnostic tonsillectomy.

Adjuvant radiotherapy or chemotherapy can be applied to cases with adverse pathologic features and in cases of advanced or incompletely resected lesions. FDCS is considered a low- or intermediate-grade malignancy.2, 3, 7-9 Previous reports characterized the criteria for a poor prognosis as follows: tumor size of > 6 cm, nuclear pleomorphism, high mitotic count (≥ 5 per 10 high-power field), intraabdominal location, lack of adjuvant therapy, coagulation necrosis, and significant cellular atypias.2, 5 In the current case, the adjuvant radiotherapy was performed due to a high mitotic count.

FDCS is a rare tumor which has been frequently described in recent studies and can be misdiagnosed at a high rate in cases which occur in extranodal sites. Accordingly, a histopathologic examination is mandatory in cases in which the mass developed in the tonsils. A differential diagnosis of a tonsillar mass should include FDCS. In cases in which FDCS is suspected on histopathologic examination, an immunohistochemical study is essential for the differential diagnosis.